Impaired hand function is a major cause of chronic disability among stroke survivors. Although a number of treatment approaches have been developed to facilitate the recovery of hand function, most target mildly impaired individuals. Efforts to rehabilitate individuals with severe impairment often treat the hand/wrist in isolation without consideration of the deleterious effects of proximal joint demands, like those experienced when lifting the arm against gravity to reach and retrieve a glass from a cabinet. Our long-term goal is to bring effective therapeutic strategies to those with moderate to severe hand impairment. To do this we have focused on the role of abnormal joint coupling in arm functioning. Following the loss of corticospinal tract fibers, movement in individuals with stroke s impaired by stereotypic multi-joint movement patterns (synergies) that result in the loss of independent joint control. For instance in the paretic arm, shoulder abduction is abnormally coupled with elbow flexion (flexor-synergy). As part of the first cycle of this R01 (years 1-5), we quantified torque-coupling patterns, and associated muscle activations, isometrically by using a 6 Degree-of-Freedom load cell. We also discovered that multi-joint isometric efforts were constrained to these abnormal coupling patterns. As part of the second cycle of this R01 (years 6-10), we progressed the work into dynamics, utilizing robotic devices to establish that reaching work area is reduced as a function of increasing abduction loading, and conducting robotic joint perturbation studies to demonstrate the integrated nature of the loss of independent joint control and vibration reflexes. Finally, recent work using the asymmetric tonic reflex and transcranial magnetic stimulation to probe brainstem excitability has provided evidence of increase reliance on the ipsilateral reticular formation, presumably through the reticulospinal tract, as the source of loss of independent joint control. The overall goal of the current renewal (years 11-15) is to further our understanding of the effects of the flexion synergy on wrist/hand function and the underlying neurophysiology. To do this we will determine the extent to which isometric shoulder abduction effort (Aim 1) and functional arm reaching (Aim 2) alter muscle activation during isometric hand muscle activations. These studies will inform our third approach to detect the intention behind actual hand movements and ultimately determine the impact of the flexion synergy on dynamic wrist/finger movement (Aim 3). Detecting wrist/hand movement intent within the context of a quantitatively controlled whole-limb movement in individuals with moderate to severe impairment is innovative and has the potential to propel the field vertically. We will use the results from Aims 1-3 to develop an effective algorithm for detecting hand opening, closing, and relaxation, a key component in restoring function to the paretic hand in individuals with moderate to severe impairment following stroke. Thus, the outcome of this study is expected to have a crucial impact on future rehabilitation approaches even for the most severely impaired stroke survivors.